Citation

Kuhn-Nentwig L, Fedorova IM, Lüscher BP, Kopp LS, Trachsel C, Schaller J, Vu XL, Seebeck T, Streitberger K, Nentwig W, Sigel E, Magazanik LG. J. Biol. Chem. 2012; 287(30): 25640-25649.

Affiliation

University of Bern, Switzerland;

Copyright

(Copyright © 2012, American Society for Biochemistry and Molecular Biology)

DOI

10.1074/jbc.M112.339051

PMID

22613721

Abstract

CsTx-1, a pore-former CsTx-1, the main neurotoxic acting peptide in the venom of the spider Cupiennius salei is composed of 74 amino acid residues, exhibits an ICK motif and is further characterised by its highly cationic charged C-terminus. Venom gland cDNA library analysis predicted for CsTx-1 precursor a prepropeptide structure. In the presence of trifluoroethanol, CsTx-1 and the long C-terminal part alone (CT1-long; Gly45-Lys74) exhibit an α-helical structure, as determined by CD-measurements. CsTx-1 and CT1-long are insecticidal towards Drosophila flies and destroys Escherichia coli SBS 363 cells. CsTx-1 causes a stable and irreversible depolarisation of insect larvae muscle cells and frog neuromuscular preparations which seem to be receptor independent. Furthermore, this membranolytic activity could be measured for Xenopus oocytes, in which CsTx-1 and CT1-long increase ion permeability non-specifically. These results support our assumption that the membranolytic activities of CsTx-1 are caused by its C-terminal tail, CT1-long. Together, CsTx-1 exhibits two different functions: as a neurotoxin it inhibits L-type Ca2+-channels and as a membranolytic peptide it destroys a variety of prokaryotic and eukaryotic cell membranes. Such a dualism is discussed as an important new mechanism for the evolution of spider venomous peptides.

Language: en